Crescent Biopharma, Inc. (CBIO) May 13, 2026 Conference Transcript

Hey, everyone. My name is Matthew Guggenmiller. I'm an associate on Alex Drenahan's mid-biotech team at B of A. Pleased to be joined with Crescent Biopharma with Joshua Brom, the CEO, and LEM, the CMO. Thanks for joining us, guys. Thanks for the invitation. Yeah, maybe just at a high level for a couple of minutes, just could you introduce, you know, the company's sort of PD-1, VEGF space, and sort of the recent developments, what you're looking forward to?

Yeah, for sure. I mean, look, I think Crescent's vision is to build the world's next leading biotech oncology company. and we do that through a two-pronged approach. The first approach is on our next-gen foundational IO by-specific program, CR001. And the other side of the coin there is our ADC portfolio and really with our vision towards winning in the frontline setting in various tumor types and indications around synergistic combinations. And so that's been the strategy for the company for quite some time. We have started this year in the clinic with our first program 001 which went in and started dosing patients in early q1 our second program which is partnered with colune for our first adc our ib6 topo adc cr003 it is now in the clinic dosing patients as well and then yesterday colune announced that our o1 program was a ind was accepted in china so it's starting there as well and so we've got three inds cleared so far this year our second program are in our adc uh stable our 002 asset our pdl1 topo adc will be in the clinic middle of this year and we plan to start at least four clinical studies across those three programs this year and so we're in a really good position to drive towards real data creation starting q127 with the o1 program the o3 program in china and we're really up for a real nice run of robust data coming and starting q127 yeah that's helpful maybe you know at a high level i think when people think pd1 veges most people think lung cancer i guess you know there's potential for 40 50 potential label indications maybe even more how do you guys decide which indications to prioritize in development and commercial opportunity as a sort of following pembro's path yeah i mean look i think i'll let ellie uh talk about this a little bit too but But what we've been out saying is that in our O-1 program, we're focused on generating three buckets of data by mid-27. The first bucket of data from our SEND study will be from our backfill cohorts, which will be our first-line non-small cell frontline data. And I think that's going to be really important for us to validate clinically, you know, how we design this molecule to be similar to Ivanosimab. We've seen that from a pre-collectual perspective, but now having the clinical data to replicate that will be really important. And that first bucket of data would be Q127. The second bucket of data that we're really focused on is looking at O1 combination with standard care chemo, multiple chemo agents across multiple indications, you know, 12 plus patients per arm. So we can really get a robust response and really validate that we can work and combine O1 across multiple chemo agents and think about getting back to your question, where we want to take the program from a registrational perspective and what indications. the third bucket will be through our clune partnership and the adc combo with oh one which will announce uh that that study at least one study that'll start this year sometime in q3 q4 and so we're really going to be guided to know what indications we want to go into by data and so driving towards those three buckets of data by mid-27 will really enable us to have the data in hand as well as monitoring the competitive landscape on where we want to go with our program um and it's not just the 01 program but it's also the 01 program plus ADCs in combination so we'll really step back and look at where we can make the biggest impact where we can think about being first in class versus best in class and let the data drive those decisions yeah that's helpful and maybe speaking about that q127 data package can you just maybe speak to you know patient numbers follow-up durability that we expect to see in that and then maybe you know how important it is that you're showing first line uh data whereas you know typically you see later line uh studies first and then movement into earlier lines sure i'll just quickly say that look we understand the value of creating meaningful data so what we didn't want to do is spend time debating second line plus data with others that have been out there before we know that data anywhere from 12 to 25 response rates it depended on if you had pd1 pre-treatment, what line of therapy you came from, and how many percents of those patients per line of therapy were in that data set. We really wanted to be able to quickly identify efficacy and separate, and that's why we wanted to show that first line non-small cell. As far as what we expect to see and some of the patient numbers, I'll let Ellie talk about the Ascend study a little bit.

Yeah, so we have a global phase 1-2 trial of CR-001, our PD-1 VEGF, by specific studying eight different indications. lung cancer, and then GI, as well as a guide on indications. The data that we will present early next year will have a very comprehensive safety tolerability, efficacy, PK, and pharmacodynamics data from our dose escalation, as well as a tumor-type specific backfills. So as we are escalating the dose, for example, we have 3, 10, 20, and 30 mcg per kick. So as we are clearing these dose levels, we have opportunity to open tumor-type specific backfill cohorts, for example, non-small cell lung backfill, colorectal backfill, or endometrial backfill. And so this is an iterative process that we can generate multiple number of patients' data at each dose level, and it will include frontline non-small cell lung cancer data as well. So with this data set being shared in early 2027, we will then have clinical data to really compare how CR001 is working compared to IVANESMEP as well as other leading PD-1 VEGF by specifics.

Yeah, that's helpful. And then, you know, when we think about the PDX-VEGF space, I think a big debate is always, you know, sort of global data, Western data versus, you know, China data. I guess, what are your thoughts on that? And, you know, given you guys are running a global trial, is that an advantage for you? And then sort of maybe thinking about, let's say the data looks good. I guess what's the path forward to registration? You know, is it, you know, all shots on goal? How do you think about capital allocation, potential partnership as well?

Why don't you talk about Harmony 6 a bit and the read-through that we get asked quite a bit around, you know, what does that mean for Western patients versus Chinese patients and the discounts that people are trying to apply there? I think, you know, probably not a great idea to do that. so maybe let's walk through some of that data and then I'll talk about the capital allocation.

Regarding your question, I think that's one of the biggest questions that's out there as well as the overall survival benefit of this class. So for us, it's great that we are running a global trial of ASCEND. It's studied in the United States, Europe, as well as Asia-Pac. But we also have our partner in China, Kulun. They will do CR001 phase one trial as well. So we are generating meaningful data from China as well as a global stage. What's great about this is that we don't have to worry about data translatability and then working with the FDA, now the different endpoints and how to do the registration trials and powering all those things that we are seeing some of the difficulties that we are seeing with the summit case. So we don't have to worry about any of those things as we are learning all the great lessons from Summit and others that are ahead of us. To Josh's point, now we are anticipating Harmony 6 Oval Survival Data at ASCO Plenary Session, which is really exciting. and a lot of questions that we are getting is a HARMONY-3 trial, which is the same population that's studied in the global setting, squamous non-small cell lung cancer patients in combination with chemotherapy. And what we are seeing so far is that HARMONY study, which is a global study, they studied the EGFR mutated non-small cell lung cancer patients Compared to the study, Harmony AIDS study, the same population done in China, we are seeing great translatability of survival benefit between Chinese population and the Western population. And we are also seeing meta-analysis data coming from global phase three oncology studies. is survival benefit perspective, Asian patients, and the global population, that translatability is quite good. So overall, we feel really confident about PD-1-VEGF as a class, and then the data translatability that we will see, and more and more data coming out, everybody, including the patients, investigators, investors, as well as the farmers and strategics, we are gaining a lot of confidence that this is a next-generation IO backbone that has a full potential to replace PD-1 inhibitors.

Yeah, that's helpful. And then maybe, you know, on the link between PFS benefit and OS benefit, I guess just thinking long-term about, you know, what bar you need to see versus PD-1s to see, you know, uptake. And then I guess looking at the PD-1 VEGF class as a whole, you know, is it sort of a one winner takes all space or do you think there's optionality for multiple players to compete across, you know, the potential 40 to 50 indications?

Yeah, I mean, I think our experience is telling us in the field, right, having now dose patients been in the clinic, working with investigators, it's about clinical benefit, right? And so I think we feel like four more months of benefit is enough for people to get really excited about this and see this, you know, new class of drugs kind of replace the first generation PD-1s. And so I think that's what we're kind of looking for, some of this data that we're going to come see at ASCO. And, you know, I think that puts us in a great position with our strategy with O1 and how we've designed these studies. And I think, you know, it's very, very much a focus of ours to generate that data and be in a position to really be a best in class by a specific partner choice with our O1 program by the middle of next year by generating data across the three buckets and having the design of the molecule replicate the Cooperative Pharmacology of Ivanesimab. I think that's the key piece that we are looking to win on long term. And I don't think it's a win or take all strategy. I think if we can replicate the cooperative pharmacology and the clinical results of Ivanesimab and the safety of Ivanesimab in the clinic, I think that, you know, you mentioned earlier 40 plus indications that are unlabeled for PD-1s now, the opportunity and indications like CRC where you see label expansion and some of the nice data there in the phase two studies in crc in china 80 plus percent response rates with the bispecifics i think those are areas in combination with with chemo standard of care i think those are some of the opportunities where there's just so many ways to go whether you want to be first in class in an area where people aren't working that with bispecifics right now in combination standard care like endometrial one that l is quite familiar with or you want to go in combination therapy and go win and and non-small cells so i think all of it's open it's just a matter of where you want to place your bets and um and how you want to devise your own clinical strategy but plenty of ways to win here yeah that's helpful and maybe switching to the partnership with kaylun um you know i guess a big debate in the space has been sort of chinese biotech and the speed of development there i guess can you speak to how your partnership maybe allows you to quickly inform go no-go decisions uh for ex-china development yeah i mean look i think uh first of all we really appreciate our partnership I think it's a unique partnership, and I think people are just now starting to understand the value of what this partnership could potentially deliver. I think that, you know, I encourage you to talk to Skoloon as well. I think we both are working extraordinarily quickly. I think that they are also pleased with the speed at which we're working, and I think together we're working at a pretty rapid clip. And so I do think that, as Ellie mentioned, you know, we have the ability to start the study globally of the O-1, kind of getting around some of the issues that previous, you know, people have had to deal with in the space. I think having the supplemental data from O-1 from China is going to be helpful. But having them run the O-3 program, our IB6, Topo ADC, which we're really excited about, and China early, and then getting that data and thinking about how and when we file the IND, how we move forward quickly here with our development outside of Greater China with O3 and in combination with O1 is something that really doesn't allow us to accelerate that development, maybe shaves off one to two years of development timeline. So it's a really good partnership, and we have the ability to work together to find the best ways to bring these combination strategies forward for patients.

Yeah, that's helpful. And you mentioned 003, the integrin beta 6 topo ADC, which is already in phase one in China with data expected Q1 of 27. I think you designed it with superior internalization and low expressing cells and a stable linker to reduce toxicity. I guess, how does that optimization over prior programs translate into a differentiated clinical profile? And, you know, can you frame what we can expect in that readout in Q1 in terms of tumor types, patient number, follow up, et cetera?

Yeah, so we intentionally designed that Irogin Beta 6, and Colun did a really great job. And Colun is known for their expertise in building quality ADCs, such as the SEC-TMT. And so when it comes to antibody of ADC, it's about internalization, how you can internalize and then release that cytotoxic payload. And to your point, they use the antibody that have potentially superior internalization power, not just in the high express cells, but in lower express cells as well. So that can overcome the issues around the tumor heterogeneity. And then with the more stable linker that they have used, it can reduce the risk of systemic toxicity as well as releasing free payload in the systemic blood. And the topo payload that we have is an excellent bystander effect and, of course, is known to have a wider therapeutic index compared to some of the other payloads that are out there, such as MMAE. So all this differentiation that Kulun put in, and we love this asset for that, it gives us a great chance to create differentiated efficacy profile, not just in non-small cell lung cancer where Pfizer is doing phase 3 trial which is the readout planned for the middle of this year but additional indications as well and also we have opportunity to combine with CR001 which is PD-1-DGF so we can win as a monotherapy as well as in combination in multiple indications.

Yeah, that's helpful and I think we're unfortunately at time but I wanted to thank both Joshua and Ellie for the great conversation today and looking forward to all the updates in the space, both from you guys and broadly. So thanks again.

Thank you so much.